Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203)

Han, Chun; Ye, Sisi; Hu, Chunhong; Shen, Liangfang; Qin, Qian; Bai, Yuxian; Yang, Shaoxing; Bai, Chunmei; Zang, Aimin; Jiao, Shunchang; Li, Bai

doi:10.3389/fonc.2021.684867

Cited by 48 publications

(36 citation statements)

References 32 publications

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“…Sintilimab plus anlotinib had an ORR of 35.0% per RECIST v1.1, which is consistent with other combination regimens of an ICI and an antiangiogenic TKI such as in the KEYNOTE-524 trial ( 18 ), the RESCUE trial ( 26 ), and the AK105-203 trial ( 29 ), which achieved an ORR between 31% and 36%. Meanwhile, sintilimab plus bevacizumab in the ORIENT-32 study had an ORR of 20.0% and atezolizumab plus bevacizumab yielded an ORR of 27.3% in the milestone IMbrave150 study ( 16 , 30 ), suggesting that small molecule inhibitors of oncoangiogenesis might be more effective than antiangiogenic monoclonal antibodies in enhancing patient treatment response when in combination with an ICI.…”

Section: Discussionsupporting

confidence: 80%

Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study

Chen

et al. 2022

Front. Oncol.

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PurposeImmune checkpoint inhibitors plus antiangiogenic tyrosine kinase inhibitors may offer a first-line treatment for advanced hepatocellular carcinoma (HCC). In this phase 2 trial [registered with clinicaltrials.gov (NCT04052152)], we investigated the safety and efficacy of first-line anti-PD-1 antibody sintilimab plus antiangiogenic TKI anlotinib for advanced HCC.Methods and MaterialsPathologically-proven advanced HCC patients received sintilimab (200 mg) on day 1 and anlotinib (12 mg) once daily on days 1 to 14 every 3 weeks, with a safety run-in for the first six participants to assess dose-limiting toxicities (DLTs). The primary endpoints were safety and objective response rate (ORR) per RECIST v1.1.ResultsTwenty advanced HCC patients were enrolled. No DLTs occurred in the safety run-in. All patients had treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 8 (40.0%) patients, the most common being decreased platelet count (10.0%) and increased γ-glutamyl transferase (10.0%). No grade 4/5 TRAEs occurred. Five (25%) patients developed immune-related AEs. The ORR was 35.0% (95%CI 15.4%-59.2%) per RECIST v1.1 and 55.0% (95%CI 31.5%-76.9%) per modified RECIST. At data cutoff (March 31, 2021), the median progression-free survival was 12.2 months (95%CI, 3.8 to not reached). The median PFS was significantly longer in patients with lower LDH levels (not reached [NR], 95% CI, 8.7 to NR vs. higher LDH levels 5.2 months, 95% CI 3.4 to NR; P=0.020) and a CONUT score ≤2 (NR, 95% CI 5.1 to NR vs. CONUT score >2 6.2 months, 95% CI 1.8 to NR; P=0.020). Furthermore, patients showing tumor response had a significantly higher median proportion of CD16+CD56+ NK cells than patients who had stable or progressive disease (21.6% vs. 14.6%; P=0.026).ConclusionSintilimab plus anlotinib showed promising clinical activities with manageable toxicity as first-line treatment of advanced HCC.

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Section: Discussionsupporting

confidence: 80%

Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study

Chen

et al. 2022

Front. Oncol.

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“… 24 Besides, penpulimab (a humanized anti-PD-1 antibody) plus anlotinib demonstrated an ORR of 31.0%, a DCR of 82.8%, and a median PFS of 8.8 months (95% CI, 4.0–12.3) after the first-line treatment in Chinese patients with unresectable HCC. 25 In the present study, anlotinib and PD-1 blockades combination therapy resulted in an encouraging ORR of 28.57% and a DCR of 71.43%, which was comparable to previously combination therapy or PD-1/PD-L1 monotherapy. However, anlotinib and PD-1 blockade combination therapy in our study not tended to yield a favorable efficacy than anlotinib monotherapy in terms of ORR, DCR, PFS, and OS (all p >0.05).…”

Section: Discussionsupporting

confidence: 79%

“… 23 Although several phase II studies have confirmed the clinical benefit of anti-PD-1 monotherapy (sintilimab or penpulimab) plus anlotinib for advanced or unresectable HCC, both studies were performed in the first-line setting. 24 , 25 Evidence of anlotinib combined with anti-PD-1 monotherapy as second-line or further therapy in advanced HCC is still scanty currently, especially in the real-world setting. Thus, a retrospective, real-world study was conducted to evaluate the effectiveness and safety of anlotinib with or without PD-1 blockades as first-line or further therapy for Chinese patients with advanced primary HCC.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China

Chen¹,

Zhao²,

Zhang³

et al. 2022

DDDT

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Purpose Anlotinib, a novel multi-target tyrosine kinase inhibitor, has shown encouraging antitumor effects in advanced hepatocellular carcinoma (HCC). This study evaluated the effectiveness and safety of anlotinib with or without programmed death-1 (PD-1) blockades for patients with advanced primary HCC in a real-world setting in China. Patients and Methods Between July 2019 and May 2021, 27 patients with advanced primary HCC who received at least 2 cycles of anlotinib were included in this retrospective study. Primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results Of the 27 patients, ORR and DCR were 25.93% and 74.07%, respectively. The median follow-up time was 6.27 months (range: 1.30–17.40) with a median PFS and OS of 3.29 months (95% CI: 1.31–15.47) and 6.21 months (95% CI: 2.23–15.87), respectively. A total of 14 patients received anlotinib and PD-1 blockade combination therapy, and 13 received anlotinib monotherapy. No significant differences were observed in ORR (28.57 vs 23.08%), DCR (71.43 vs 76.92%), PFS (3.38 [95% CI: 2.66–13.14] vs 11.86 months [95% CI: 4.27–15.93]) and OS (4.90 [95% CI: 2.56–13.60] vs 11.04 months [95% CI: 1.31–17.18]) between the two groups (all p >0.05). Treatment-related AEs were reported in 88.89% of patients. Grade 3 AE was bleeding, which occurred in 3 patients (11.11%). Conclusion Anlotinib yielded a promising efficacy and manageable safety in patients with advanced primary HCC irrespective of whether patients received PD-1 blockades, indicating that anlotinib might be a promising treatment option for this patient population.

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“…In 31 patients evaluated based on the RECIST 1.1 criteria, the first-line treatment of hepatocellular carcinoma with anlotinib in combination with penpulimab achieved an overall response rate (ORR) of 31%, a disease control rate (DCR) of nearly 83%, and a median progression-free survival (PFS) of 8.8 months, which was comparable to the efficacy of similar anti-angiogenic therapy and immunotherapy combinations. Adverse effects were manageable, and the safety profile was deemed satisfactory ( 11 ). Similarly, studies on the treatment of ES-SCLC have repeatedly reported the clinical benefits of this drug combination approach.…”

Section: Introductionmentioning

confidence: 99%

Successful Treatment of a Patient With Multiple-Line Relapsed Extensive-Stage Small-Cell Lung Cancer Receiving Penpulimab Combined With Anlotinib: A Case Report

Zhang

Dong

et al. 2022

Front. Oncol.

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Small-cell lung cancer (SCLC) is a highly malignant, rapidly developing group of diseases with poor biological behavior. Most patients have extensive-stage SCLC (ES-SCLC) when they are first diagnosed. Standard chemotherapy is prone to relapse in a short period of time, and the patients’ median overall survival (OS) can reach only 13 months when chemotherapy is given in combination with PD-L1 inhibitors. To date, no studies have verified the efficacy and safety of the composite treatment of ES-SCLC with penpulimab and anlotinib despite some recognized data and advantages related to this regimen. Penpulimab, a novel PD-1 inhibitor with an IgG1 subtype, has a structural modification of the Fc segment which can prevent the immune cells from being phagocytosed or killed and can steadily avoid tumor immune escape. This case report describes a 71-year-old man who had ES-SCLC for 7 years which progressed after receiving standard systemic chemotherapy combined with radiotherapy. The third-line treatment of four cycles of anlotinib and carilizumab was discontinued because of grade 2 immune-related pneumonia despite the efficacy being evaluated as stable disease. After maintaining 22 months of progression-free survival, the patient relapsed and switched to a safer regimen of penpulimab combined with anlotinib to continue the treatment for four cycles. Partial response evaluation was confirmed twice, and the patient remained in good general condition. The combination of penpulimab and anlotinib can positively regulate the therapeutic effect by simultaneously acting on the tumor microenvironment and promoting blood vessel normalization. In general, this case provides support for the successful possibility of a rechallenge with immune checkpoint inhibitors, the better clinical efficacy of cross-line therapy with anlotinib, and the drug safety of penpulimab, suggesting a beneficial therapy for the clinical treatment of ES-SCLC.

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Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203)

Cited by 48 publications

References 32 publications

Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study

Safety and Efficacy of Sintilimab and Anlotinib as First Line Treatment for Advanced Hepatocellular Carcinoma (KEEP-G04): A Single-Arm Phase 2 Study

Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China

Successful Treatment of a Patient With Multiple-Line Relapsed Extensive-Stage Small-Cell Lung Cancer Receiving Penpulimab Combined With Anlotinib: A Case Report

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